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SUMMARY:Crick Lecture- The transformative CRISPR-Cas9 genome engineering t
 echnology: lessons learned from bacteria - Emmanuelle Charpentier 
DTSTART:20151002T141500Z
DTEND:20151002T151500Z
UID:TALK60117@talks.cam.ac.uk
CONTACT:Scientific Meetings Co-ordinator
DESCRIPTION:The RNA-programmable CRISPR-Cas9 system has recently emerged a
 s a transformative technology in biological sciences\, allowing rapid and 
 efficient targeted genome editing\, chromosomal marking and gene regulatio
 n in a large variety of cells and organisms. In this system\, the endonucl
 ease Cas9 or catalytically inactive Cas9 variants are programmed with sing
 le guide RNAs (sgRNAs) to target site-specifically any DNA sequence of int
 erest given the presence of a short sequence (Protospacer Adjacent Motif\,
  PAM) juxtaposed to the complementary region between the sgRNA and target 
 DNA.\n\nOriginally\, CRISPR-Cas is an RNA-mediated adaptive immune system 
 that protects bacteria and archaea from invading mobile genetic elements. 
 Short crRNA (CRISPR RNA) molecules containing unique genome-targeting spac
 ers guide Cas protein(s) to invading cognate nucleic acids to affect their
  maintenance. CRISPR-Cas has been classified into three main types and fur
 ther subtypes. CRISPR-Cas9 originates from the type II system that has evo
 lved unique molecular mechanisms for maturation of crRNAs and targeting of
  invading DNA\, which my laboratory has identified in the human pathogen S
 treptococcus pyogenes. During the step of crRNA biogenesis\, a unique CRIS
 PR-associated RNA\, tracrRNA\, base pairs with the repeats of precursor-cr
 RNA to form anti-repeat-repeat dual-RNAs that are cleaved by RNase III in 
 the presence of Cas9\, generating mature tracrRNA and intermediate forms o
 f crRNAs. Following a second maturation event\, the mature dual-tracrRNA-c
 rRNAs guide Cas9 to cleave cognate target DNA and thereby affect the maint
 enance of invading genomes. We have shown that Cas9 can be programmed with
  sgRNAs mimicking the natural dual-tracrRNA-crRNAs to target site-specific
 ally any DNA sequence of interest. I will discuss the biological roles of 
 CRISPR-Cas9\, the mechanisms involved\, the evolution of type II CRISPR-Ca
 s components in bacteria and the applications of CRISPR-Cas9 as a novel ge
 nome engineering technology.\n
LOCATION:Max Perutz Lecture Theatre\, Medical Research Council (MRC) (MRC 
 Laboratory of Molecular Biol
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